Blast Crisis

Audience This scenario was developed to educate emergency medicine residents on the diagnosis and management of blast crisis. Introduction Chronic myeloid leukemia (CML) makes up 15% of diagnosed adult leukemias with the median age of diagnosis being 67 years old. Chronic myeloid leukemia consists of three phases: chronic, accelerated, and blast phases. Most patients are initially diagnosed while in the chronic phase.1 Of those diagnosed in the chronic phase and being treated with a tyrosine kinase inhibitor (TKI), about 1% –1.5% of CML patients per year will subsequently transform into an advanced phase or blast crisis.2 While rare, blast crisis is considered an oncologic emergency, with increased mortality occurring primarily from subsequent infections or bleeding. Therefore, emergency physicians must be familiar with its clinical presentation and subsequent management. Educational Objectives By the end of this simulation, the participant will be able to: 1) create a thorough differential for the undifferentiated febrile, altered patient, 2) identify the signs and symptoms of blast crisis, 3) describe proper resuscitation of a patient in blast crisis, and 4) describe the indications, steps, and contraindications of performing a lumbar puncture. Educational Methods This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on the diagnosis, differential diagnosis, and management of blast crisis. Debriefing methods may be left to the discretion of participants, but the authors have used advocacy-inquiry techniques. This scenario may also be run as an oral boards case. Research Methods Our simulation center’s feedback form is based on the Center of Medical Simulation’s Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form, with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. Results This session received all 6 or 7 scores (consistently effective/very good or extremely effective/outstanding). During the debriefing session, feedback from the residents was largely positive. They appreciated reviewing the broad differential of altered mental status and oncologic emergencies. While many groups anchored on the diagnosis of encephalitis, they also expressed that after this experience, blast crisis would be added to their differential for patients with CML. Discussion This is a cost-effective method for reviewing blast crisis. Learners were able to identify more common causes of altered mental status in their differentials, but without further prompting, they were unable to ultimately come up with the diagnosis of blast crisis. Our main take-away is to continue reviewing oncologic emergencies as a part of our residency curriculum. Topics Medical simulation, chronic myeloid leukemia, blast crisis, leukostasis, emergency medicine, oncologic emergencies, hematologic emergencies.


Recommended pre-reading for instructor:
We recommend that instructors review literature regarding blast crisis, including epidemiology, presenting signs/symptoms, diagnosis, and management. High-yield readings include the following: •

Results and tips for successful implementation:
This simulation scenario was conducted approximately three times for a total of eight emergency medicine residents. We found that the residents struggled to make the diagnosis. While other groups entertained the potential for encephalitis, all three groups were unable to come up with the diagnosis even when provided the CBC and pertinent history. Some groups were able to identify that lumbar puncture would likely be contraindicated due to the patient's thrombocytopenia. During the debriefing, it was discovered that blast crisis was considered by some individuals in two of the groups' differentials but was ultimately not voiced to the rest of the group. The residents were able to come up with other oncologic emergencies in their differentials such as tumor lysis syndrome, but they were less familiar with blast crisis and the appropriate management.
Our simulation center's feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. This session received all 6 or 7 scores (consistently effective/very good or extremely effective/outstanding). Mean scores are as follows: Category 1 (the instructor set the stage for an engaging learning experience) 6.125, Category 2 (the instructor maintained an engaging context for learning) 6.375, Category 3 (the instructor structured the debriefing in an organized way) 6.5, Category 4 (the instructor provoked in-depth discussions that led me to reflect on my performance) 6.25, Category 5 (the instructor identified what I did well or poorly -and why) 6.125, and Category 6 (the instructor helped me see how to improve or how to sustain good performance) 6.25. Our form also includes an area for general feedback about the case at the end. Comments included "Good case; would have liked patient to have hard signs of end organ damage such as stroke or Background and brief information: Patient is a 64-year-old male who is brought in by his wife for a day of confusion.
Initial presentation: Per his wife, he has been acting confused all day today. He seems confused about where he is and what year it is. He has been sleepier for the past two days and also complains of headache, general pains, and chills. His wife took his temperature today and noted a fever of 101°F. He was recently diagnosed with CML, but treatment has not yet been initiated.
How the scenario unfolds: Patient is a 64-year-old male who is brought into the emergency department (ED) by his wife for a headache. He is altered, so additional history is obtained from his wife. He also has been having fevers, vision changes, and confusion. Goals include early recognition of blast crisis and evaluation of other causes of alerted mental status in the undifferentiated febrile patient. Participants should obtain a peripheral smear, bloodwork, a chest x-ray, and urinalysis. Once patient receives an antipyretic and an IV fluid bolus, fever and heart rate will improve. If participants proceed with a lumbar puncture despite thrombocytopenia, patient will report back pain and leg weakness. Once the diagnosis of blast crisis is made, hematology should be immediately consulted for emergent assessment for TKI therapy and leukapheresis. In the meantime, the patient should be placed on the appropriate antibiotics for possible confounding or concurrent infectious etiologies. The patient should be admitted to the intensive care unit (ICU). (A) If team performs an LP, patient will complain of low back pain and state "something is wrong with my legs." Patient will now have 2/5 strength in bilateral lower extremity. The wife will insist that the participants tell her why his legs are now weak.
(B) If the hospitalist/intensivist is contacted prior to talking to hematology, they will ask the team to do so given the patient's history of CML.

Pearls:
Chronic myeloid leukemia makes up 15%-20% of adult leukemias. CML is characterized by the BCR-ABL fusion gene and the creation of the Philadelphia chromosome. The natural history of myeloid leukemia is characterized by three phases: chronic, accelerated and blast phase. 3 The progression of CML to blast crisis has been reduced to 1% to 1.5% per year compared to greater than 20% a year in the pre-imatinib era. 2 Blast crisis is a life-threatening condition characterized by in the increase in blastic cells resulting in hyperviscosity and relative reduction of the other cell lines. The common laboratory features of blast crisis include high white blood cell and blast counts, as well as decreased hemoglobin and platelet counts.
The World Health Organization defines blast crisis as the presence of one or more of the following findings: 20% or greater peripheral blood or bone marrow blasts, large foci or clusters of blasts on bone marrow biopsy, or the presence of extramedullary blastic infiltrates. 3 Patients who have progressed to the blast phase may present with fever, poor appetite, night sweats, bone pain and weight loss. Therefore, what used to be a chronic leukemia now presents like an acute leukemia. 4 Hyperleukocytosis is defined as a WBC above 100,000/µL due to leukemic cell proliferation. This can lead to complications such as leukostasis, tumor lysis syndrome, and disseminated intravascular coagulation. 6 Leukostasis is a clinical diagnosis as a result from blood hyperviscosity and the formation of WBC plugs in the microvasculature. These plugs subsequently lead to decreased tissue perfusion which may lead to end-organ damage. All the immature precursor cells "crowd out" other cell lines, leading to functional anemia, thrombocytopenia, and neutropenia.
The most common cause of death in blast crisis is an infection due to functional neutropenia, followed by hemorrhage due to functional thrombocytopenia. Leukostasis requires emergent treatment and placement in an intensive care unit for aggressive monitoring.
Patients may present with a variety of symptoms affecting many systems due to leukostasis. Most commonly, patients in blast crisis present with neurologic or respiratory complaints. 6 They may also develop acute coronary syndromes, limb ischemia, bowel infarction, renal insufficiency, and priapism. Extramedullary blast crisis occurs when leukemic blasts infiltrate areas outside of bone marrow, such as the paravertebral scalp to cause spinal cord compression, leukemic ascites, eyes to cause enucleation, and osteolytic bone lesions. Patients will require a broad work up to rule out other potential causes of their symptoms. In this case, the patient presented with neurologic complaints secondary to leukostasis. Common neurologic complaints include visual changes, headache, dizziness, tinnitus, gait instability and confusion. Without a thorough work-up, other diagnoses such as stroke, meningitis, and encephalitis cannot be excluded.

DEBRIEFING AND EVALUATION PEARLS
Overall, the emergency provider should treat any sign of infection with broad spectrum antibiotics. Fever may be due to leukostasis or concurrent infection. The patient should be adequately fluid resuscitated while work up is ensuing. According to the NCI's PDQ cancer information summary about CML: treatment in the blast phase consists of TKIs, chemotherapy, hydroxyurea, and bone marrow transplantation. TKI therapy consists of Imatinib, Dasatinib, and Nilotinib. Two trials involving Imatinib and one trial with Dasatinib showed a hematologic response rate of 42% to 55% and a major cytogenetic response rate of 16% to 25%. Often TKIs may be combined with a chemotherapy agent such as Vincristine and prednisone. Bone marrow transplantation is the only potentially curative therapy for these patients. Bone marrow transplant is more effective in those patients who can be induced into a second chronic phase. 5

Other debriefing Points:
As an emergency medicine provider, it is important to know your state laws when obtaining consent from the next of kin. When a patient lacks the capacity to make their own medical decisions, the next of kin should be the one to provide consent. Depending on your state laws and the situation, the next of kin may be a spouse or a child. In the case that a health care power of attorney is designated, this person becomes the appropriate person from whom to obtain consent. When obtaining consent, it is important to discuss the diagnosis, indications, benefits, risks and alternatives, so that an informed decision can be made. 7 This case can also be used to review the steps, indications and contraindications to performing a lumbar puncture (LP). Contraindications include increased intracranial pressure due to a central nervous system lesion, ongoing anticoagulant therapy, or overlying skin infection. After consent is obtained, the patient should be placed in the lateral decubitus position if an opening pressure is to be obtained. The iliac crests should be palpated and used to guide in locating the L3-L4 and L4-L5 spaces. These are the safest spaces to enter your spinal needle because it is well below the conus medullaris in most patients. The overlying skin should be cleaned with alcohol and a disinfectant such as povidone-iodine. Local anesthesia with